chr2-74142024-A-T

Variant names:

• chr2-74142024-A-T
• rs702465
• NM_212552.3:c.258+248T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_212552.3(BOLA3):​c.258+248T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,210 control chromosomes in the GnomAD database, including 30,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.62 (30867 hom., cov: 33)
• Consequence: BOLA3 NM_212552.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.976
• Publications: 10 publications found

Genes affected

BOLA3 (HGNC:24415): (bolA family member 3) This gene encodes a protein that plays an essential role in the production of iron-sulfur (Fe-S) clusters for the normal maturation of lipoate-containing 2-oxoacid dehydrogenases, and for the assembly of the mitochondrial respiratory chain complexes. Mutation in this gene has been associated with multiple mitochondrial dysfunctions syndrome-2. Two alternatively spliced transcript variants encoding different isoforms with distinct subcellular localization have been reported for this gene (PMID:21944046). [provided by RefSeq, Dec 2011]

BOLA3 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• multiple mitochondrial dysfunctions syndrome 2

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 2-74142024-A-T is Benign according to our data. Variant chr2-74142024-A-T is described in ClinVar as Benign. ClinVar VariationId is 683414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212552.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLA3	NM_212552.3	MANE Select	c.258+248T>A		intron	N/A	NP_997717.2	Q53S33-1
	BOLA3	NM_001035505.2		c.169+3165T>A		intron	N/A	NP_001030582.1	Q53S33-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLA3	ENST00000327428.10	TSL:1 MANE Select	c.258+248T>A		intron	N/A	ENSP00000331369.5	Q53S33-1
	BOLA3	ENST00000295326.4	TSL:1	c.169+3165T>A		intron	N/A	ENSP00000295326.4	Q53S33-2
	BOLA3	ENST00000477685.5	TSL:1	n.409+248T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94679 AN: 152092 Hom.: 30809 Cov.: 33

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.623 AC: 94792 AN: 152210 Hom.: 30867 Cov.: 33 AF XY: 0.621 AC XY: 46231 AN XY: 74420

African (AFR) AF: 0.820 AC: 34069 AN: 41544

American (AMR) AF: 0.628 AC: 9609 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3472

East Asian (EAS) AF: 0.613 AC: 3178 AN: 5188

South Asian (SAS) AF: 0.376 AC: 1817 AN: 4830

European-Finnish (FIN) AF: 0.598 AC: 6321 AN: 10570

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36092 AN: 67990

Other (OTH) AF: 0.604 AC: 1276 AN: 2112

Alfa AF: 0.594 Hom.: 3460

Bravo AF: 0.641

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.81
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs702465; hg19: chr2-74369151;